Context: GH replacement in adult GH-deficient patients may cause insulin resistance, raising concerns of potential increased risk of developing diabetes mellitus (DM). Objective: Our objective was to assess DM prevalence and incidence in the international Hypopituitary Control and Complications Study (HypoCCS) surveillance database. Design and Participants: GH-treated patients enrolled into HypoCCS (2922 U.S. and 3709 European patients) were assessed for DM, defined as recorded on the clinical report form, reported as adverse events, fasting glucose at least 7 mmol/liter recorded at least twice, or insulin treatment reported. Results: DM prevalence was 8.2% [95% confidence interval (CI) = 7.6-8.9] overall, 11.3% in the United States and 5.7% in Europe. Incidence (n/1000 patient-years) was 9.7 (95% CI = 8.4 -10.9) overall, 14.1 (11.5-16.7) in the United States, and 7.0 (5.6-8.3) in Europe. Overall incidence was 2.1 (0.9 -3.3) for patients with body mass index (BMI) below 25 kg/m2 increasing to 16.4 (13.7-19.1) for BMI over 30 kg/m2. Obesity (BMI > 30 kg/m2) prevalence was higher in the United States than Europe and higher in U.S. patients than a U.S. reference population. After age, gender, and BMI adjustment, U.S. HypoCCS DM incidence was 10.6 (8.1-13.0), compared with 7.1 (6.0-8.1) in the National Health Interview Survey. In Europe, incidence for French and German patients was comparable to reference populations; for Sweden, the point estimate was higher than the reference population, but 95% CI overlapped. GH dose was not correlated with DM incidence. Conclusions: The present analysis showed no evidence for increased DM incidence in GH-treated adult hypopituitary patients. However, those more prone to develop DM exhibited a higher than normal prevalence of obesity. Copyright